A physiologically based pharmacokinetic model is being used to simulate the exposure of mice to methylene chloride (DCM) in a closed exposure system. Exposures performed in the closed exposure apparatus have been used to determine the rate of DCM disappearance from the test atmosphere as a function of concentration. This data is used in conjunction with the simulation to estimate whole body (global) metabolic rate constants for DCM. Measurements are being performed on animals taken from an ongoing chronic exposure at different time points to determine changes in these global rate constants as a function of both age and length of treatment. A refined model incorporating these changes will be used to provide estimates of the quantity of exposure compound and metabolites presented to target organs during the chronic exposure. The closed exposure system will be used in conjunction with the computer simulations as part of other inhalation studies to estimate the amount of exposure compound taken up by the test animals as a function of exposure concentration.